The present invention relates to a transdermal therapeutic composition designed to accelerate drug absorption through the skin and mucous membranes.
Conventional dermal administration forms such as ointments have been used ever since the the nineteenth century for the therapy of bruise, sprain, muscleache, and so on.
Recently new transdermal therapeutic systems which make possible the constant slow release of drugs, have been developed for the therapy of diseases of internal organs besides those of skin and trauma using the drugs which are quite effective even in a small amount and excellent in transdermal permeation. The well-known examples of the clinical use are the transdermal therapeutic system with nitroglycerin for the therapy of angina pectoris and with scopolamine for motion sickness. However, as these drugs permeate the skin too rapidly to invoke side-effects, such membranes as silicone and ethylene-vinyl acetate copolymers have been employed to retard and control the absorption rate of the drugs.
In addition to the two drugs, many other drugs have been tried for the transdermal administration; the examples are an unguenta form of indomethacine as an anti-inflammatory agent (Japanese Unexamined Patent Publication (Tokkyo Kokai) No. 81616/1978) and a cataplasmata form of indomethacine (Japanese Unexamined Patent Publication (Tokkyo Kokai) No. 62013/1980). Drugs for hypertension and depression as well as adrenal cortical hormones and progesterones have been also attempted for the transdermal therapeutic system. Contrary to nitroglycerin, these pharmacologically active substances have very poor transdermal permeability, so that some new means are required for enhancement of the skin absorption.
The widely attempted method for this purpose is to make the stratum corneum to become much swollen by humidifying the skin or to utilize absorption enhancers for the skin absorption. In order to swell the stratum corneum with water, it is necessary to increase the water content of the transdermal dosage form inself. Based on this principle, a dosage form of indomethacine with a high water content has been developed (Japanese Examined Patent Publication (Tokkyo Kokoku) No. 27248/1983). This is prepared from hydrogel which consists of poly(acrylic acid) crosslinked with an epoxy-type crosslinking agent. However, this matrix polymer has a problem for clinical use because of the toxicity of the crosslinking agent employed.
An object of the invention is to prepare transdermal dosage forms which are capable of making the stratum corneum much swollen in order to constantly release the pharmacologically active substances included in the forms without exerting side-effects to the body.